The long-term objective of the proposed study is to establish how molecular variation in specific proteins involved in a signal transduction pathway contributes to phenotypic variation. The project focuses on the developmental pathways associated with wing shape and photoreceptor variation in Drosophila. The general approach is to use genetic "tester" backgrounds that bear selected hypo- and hypermorphic mutations shown by Dr. Gibson to reveal modifiers of expression. He proposes that these modifiers are genes in the same signal transduction pathway that contribute to potential subtle perhaps cryptic standing genetic variation in natural populations. In these "sensitized" backgrounds measured phenotypic effects are mapped to the candidate genes of the associated EGF-Ras pathway using association or linkage disequilibrium mapping, as has been used to define QTLs for bristle variation in natural populations of D. melanogaster. The objective at this point is not to identify specific mutations responsible for functional variation yet, but to quantify relative effects of different loci in the pathway.